rs865809

Positions:

• chr3-184279947-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100121.2(ECE2):​c.816+1390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 151,960 control chromosomes in the GnomAD database, including 50,826 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50826 hom., cov: 30)
• Consequence: ECE2 NM_001100121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

Genes affected

ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ECE2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE2	NM_001100121.2	c.816+1390A>G		intron_variant		ENST00000404464.8	NP_001093591.1
EEF1AKMT4-ECE2	NM_014693.4	c.1170+1390A>G		intron_variant			NP_055508.3
ECE2	NM_001100120.2	c.954+1390A>G		intron_variant			NP_001093590.1
ECE2	NM_001037324.3	c.729+1390A>G		intron_variant			NP_001032401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE2	ENST00000404464.8	c.816+1390A>G		intron_variant		1	NM_001100121.2	ENSP00000385846.3
EEF1AKMT4-ECE2	ENST00000402825.7	c.1170+1390A>G		intron_variant		1		ENSP00000384223.3

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123316 AN: 151842 Hom.: 50771 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123419 AN: 151960 Hom.: 50826 Cov.: 30 AF XY: 0.804 AC XY: 59666 AN XY: 74252

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.827

Alfa AF: 0.788 Hom.: 36782

Bravo AF: 0.831

Asia WGS AF: 0.673 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs865809; hg19: chr3-183997735;